UVB irradiation has previously been shown to significantly increase phospholipase activity and prostaglandin synthesis. Because UVB irradiation is a potent oxidative stress, the role of active oxygen species in regulating Uv-induced cPLA2 synthesis and phosphorylation was examined. In the present study. irradiation produced a 3-fold increase in synthesis within 6 h following irradiation. Phosphorylation of cPLA2 was also increased to a similar extent. UVB-induced synthesis and phosphorylation of cPLA2 could be inhibited by pretreatment with the antioxidants 2,2,5,7,8.pentamethyl-6-hydroxychromane (50 UM) or N-acetylcysteine (lO mM). Treatment of unirradiated cultures with the potent oxidant tert-butyl hydroperoxide (500 UM) also increased cPLA2 synthesis and phosphorylation, suggesting that oxidative injury is an important regulator of cPLA2 synthesis. Increased synthesis of cPLA2 correlated well with increased (3)Harachidonic acid release, PGE2 synthesis and lipid peroxidation in epidermis after oxidant or UVB treatment. The results indicate that UVB-induced upregulation of cPLA2 synthesis is mediated by UVB-induced formation of free radicals.